Stereospecific and Non-Stereoespecific Effects of Ibuprofen on Human Platelet and Polymorphonuclear Leukocyte Functions

Villanueva, Mercy; Heckenberger, R.; Palmer, Matthew K.; Schrör, Karsten

doi:10.1007/978-3-0348-7262-1_22

Cited by 3 publications

(6 citation statements)

References 8 publications

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“…A peak concentration of 100 g/ml of ibuprofen is expected to be attained in plasma after oral intake of 1,000 mg, i.e., a dose which is lower than the maximum approved daily total dose of 1,600 mg. Also, in line with our study, Villanueva et al [10] demonstrated that racemic ibuprofen inhibited COX-related platelet aggregation and TXB 2 synthesis whereas the S-enantiomer was 40-to 100-fold more active than the R-formulation in human platelet and polymorphonuclear cells in vitro.…”

Section: Discussionsupporting

confidence: 75%

“…In particular, S-ibuprofen is speculated to be highly valuable as compared with racemic R-ibuprofen in inhibiting TXB 2 , platelets function and aggregability. As a consequence, monotherapy with S-ibuprofen instead of racemic ibuprofen use is assumed to be beneficial to patients in terms of reduced incidence of unfavorable effects such as thrombotic incidence, less drug burden and improved tolerance [10,21,24] . Thus, the present study was carried out to test (1) the effect of pure S-and R-ibuprofen and (2) different concentration ratios of their combination on TXB 2 levels in whole blood derived from drug-naive healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

“…The already well-known anti-inflammatory, analgesic and antiplatelet effects have been mainly attributed to the S-enantiomer, whereas both S-and R-enantiomers as well as their metabolites potentially cause untoward effects [8] . Current knowledge implies that the R-enantiomer is suggested to be ineffective in vivo, unless its partial inversion to the S-enantiomer, which, however, varies between species, ethnical origin and also between different organs [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

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S-Ibuprofen Effectively Inhibits Thromboxane B<sub>2</sub> Levels and Platelet Function in an Experimental Model of Lipopolysaccharide-Stimulated and Non-Stimulated Whole Blood

Kaehler

Marsik²,

Heinisch³

et al. 2007

Pharmacology

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Objective: The present study aimed at testing the effect of S- and R-ibuprofen on thromboxane B₂ (TXB₂), collagen-epinephrine closure time (CEPI-CT) and collagen-adenosine 5′-diphosphate closure time (CADP-CT) in lipopolysaccharide (LPS)-stimulated and non-stimulated human whole blood. Materials and Methods: Whole blood was incubated with S- or R-ibuprofen with and without prior stimulation with LPS. To verify ibuprofen’s potential effects on TXB₂, varying ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used. TXB₂ levels were measured by ELISA. The effects of S- and R-ibuprofen enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus. Results: In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly decreased TXB₂ levels at concentrations ranging from 10 to 200 µg/ml. R-ibuprofen showed its inhibiting effect at concentrations >100 µg/ml. In inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at concentrations of 12.5 and 75 µg/ml for S-ibuprofen and at a concentration of 150 µg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected by both enantiomers. Conclusions: S-ibuprofen was more effective than the R-ibuprofen enantiomer in inhibiting TXB₂ plasma levels and aggregability of thrombocytes in non-inflammatory and inflammatory conditions.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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S-Ibuprofen Effectively Inhibits Thromboxane B<sub>2</sub> Levels and Platelet Function in an Experimental Model of Lipopolysaccharide-Stimulated and Non-Stimulated Whole Blood

Kaehler

Marsik²,

Heinisch³

et al. 2007

Pharmacology

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“…As a corrospondíng cellular system expressing mainly COX-2, we used a primary culture ofrat mesangial cells between passagas 5 and 12 treated with interleukin-l,8 for 24 hoursv" (Figure 2B). The inhibítion was around 150 ¡¡;mol/L for S(+h about 500 ¡.tmollL for the racemíc mixture, and about 2 rnmol/L Rat mesangial cells (passages [5][6][7][8][9][10][11][12] were stiniulated [or 24 houts with 1 nmol/L interleukin-1 und incubated (N = 6 :': standard deviotiou}.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Cyclooxygenase‐1 and ‐2 by R(‐)‐ and S(+)‐Ibuprofen

Boneberg,

Zou,

Ullrich

1996

The Journal of Clinical Pharma

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Since the discovery of a cytokine‐inducible isozyme of cyclooxygenase (COX‐2), its pharmacologic inhibition has been the subject of recent investigations. These include tests for the selectivity of known nonsteroidal antiinflammatory drugs (NSAIDs) on the constitutive enzyme of cyclooxygenase (COX‐1) compared with the inducible enzyme COX‐2. The interesting question arose whether the R(—)‐ and S(+)‐isomers exhibited different inhibitory potencies for ibuprofen. Results with isolated COX‐1 and COX‐2 isozymes confirmed the known higher efficacy of S(+)‐ compared with R(‐)‐ibuprofen. The R(‐)‐isomer is almost inactive in inhibiting COX‐2. In addition, the S(+) form has a several times lower potency with COX‐2 than with COX‐1. These data were evaluated in platelets containing mainly the constitutive COX‐1, with interleukin‐1, pretreated, rat mesangial cells which almost exclusively express COX‐2.

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“…Their well-known anti-inflammatory, analgesic and antiplatelet effects have been mainly attributed to the S -enantiomer of ibuprofen, dexibuprofen, whereas both S -and R -enantiomers as well as their metabolites potentially cause untoward effects [10] . Thus, from current knowledge, the R -enantiomer is suggested to be ineffective in vivo, unless it is partially inverted to the S -enantiomer, whose effect, however, varies from one species and one organ to another, also depending on ethnical origin [11][12][13] .…”

mentioning

confidence: 99%

ADIDAC Trial: Analgesia with Dexibuprofen versus Ibuprofen in Patients Suffering from Primary Dysmenorrhea: A Crossover Trial

Kollenz

Phleps

Kaehler³

2008

Gynecol Obstet Invest

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Background: Primary dysmenorrhea is estimated to affect 40–50% of menstruating young women. Methods: Randomized, double-blind, 3-cycle crossover, active-controlled clinical trial conducted in 102 outpatients. Results: 102 patients entered the study and 77 were eligible for analyses. The mean (SD) age was 31.1 (7.0) years, and the mean cycle duration was 28.1 days (1.89) with a mean menstrual phase of 5.3 days (1.28). 40.26% of patients reported moderate pain from dysmenorrhea, and the remaining 59.74% reported severe pain. Compared to ibuprofen 400 mg, both dexibuprofen doses (200 and 300 mg) showed a trend towards superiority for sum of pain intensity difference (sum of PID), PID and total pain relief. Furthermore, dexibuprofen 200 mg had a faster onset of action compared to the double dose of ibuprofen (p = 0.035). A dose-effect relationship could be demonstrated for dexibuprofen in this visceral pain model. Tolerability was similar across all treatments. Conclusions: In patients experiencing acute visceral pain as a result of primary dysmenorrhea, dexibuprofen was associated with a dose-dependent effective analgesia; this effect was at least equivalent to that of the double dose of ibuprofen. With its lower body-loading dose, dexibuprofen expands the alternatives available to treat this condition.

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Stereospecific and Non-Stereoespecific Effects of Ibuprofen on Human Platelet and Polymorphonuclear Leukocyte Functions

Cited by 3 publications

References 8 publications

S-Ibuprofen Effectively Inhibits Thromboxane B<sub>2</sub> Levels and Platelet Function in an Experimental Model of Lipopolysaccharide-Stimulated and Non-Stimulated Whole Blood

S-Ibuprofen Effectively Inhibits Thromboxane B<sub>2</sub> Levels and Platelet Function in an Experimental Model of Lipopolysaccharide-Stimulated and Non-Stimulated Whole Blood

Inhibition of Cyclooxygenase‐1 and ‐2 by R(‐)‐ and S(+)‐Ibuprofen

ADIDAC Trial: Analgesia with Dexibuprofen versus Ibuprofen in Patients Suffering from Primary Dysmenorrhea: A Crossover Trial

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